Disorders of the central nervous system have become one of the most common and most debilitating diseases currently afflicting mankind. Specific disorders such as depression and schizophrenia are now known to be common afflictions, and are routinely diagnosed. These diseases result in significant losses of an individual's ability to work and to carry out normal daily activities, and in many cases require long term hospitalization or institutionalization. Only recently have new treatments, such as the selective serotonin re-uptake inhibitors for example, become available and are effective for many people. Unfortunately, such agents are not effective for all cases of depression, and indeed can lead to significant adverse reactions in some patients.
Other CNS disorders, such as chronic pain and seizure disorders, are only marginally treatable, and such treatments often are associated with unacceptably high health risks, for instance long term use of narcotic analgesics to treat chronic pain generally results in addiction to the drug being employed, the results of which can be devastating to the patient.
Accordingly, the need continues for new medicines that will effectively treat CNS disorders without imposing unacceptable liability and risk issues. I have now discovered a series of aromatic amides which can be utilized to treat these CNS disorders, and which have a very good risk-to-benefit ratio. The invention compounds are alkyl amides having an aromatic group attached to the amide nitrogen atom.
Several N-aryl alkylamides are known in the prior art. For example, Ronsisvalle et al. described a series of analgesic N-thienyl acetamides in Eur. J. Med. Chem. 3: 553-559, 1998.
U.S. Pat. No. 4,203,988 discloses certain N-pyridyl amide derivatives as inhibitors of gastric secretion, while U.S. Pat. No. 3,163,645 discloses N-pyridyl amides as analgesics. U.S. Pat. No. 5,372,931 discloses N-alkoxyphenyl and N-alkoxynaphtyl amides as useful in certain analytical and diagnostic methods.
Elslager et al., in J. Med. Chem. 9: 378-91, 1966, describe certain N-naphthyl amides as useful as intermediates in the synthesis of arylazo substituted naphthyl alkylenediamines. Similarly, Elslarger et al., described certain N-quinolyl amides in J. Med. Chem. 12: 600-7, 1966.
The compounds provided by this invention are characterized as novel N-aryl amides having good CNS activities, and are thus useful for treating depression, anxiety, pain, schizophrenia, and seizure disorders such as epilepsy.